Various processes for separating mixtures of different substances are used in industrial processing, engineering, biotechnology and medicinal technology to purify, concentrate, and recover specific substances. Examples of such processes are those well-known methods, extraction, distillation, freeze-drying, precipitation and chromatographic separation. In medicinal technology, hematology in particular, centrifugal processes have been utilized for separating solid blood ingredients from plasma; such processes, generally called plasmapheresis, were developed in 1959 J. L. Tullis; D. M. Surgenor; R. J. Tinch; M. D'Hont "New Principle of closed system centrifugation", Science 24, 792, (1956). In the past ten years, plasmaphersis has been supplemented in medicinal technology as well as in biotechnology by membrane separation techniques. Membrane separation provides a less disruptive process for the separation of suspended particles which often are very sensitive. In medicinal technology the process is called membrane plasmapheresis and in chemistry and biotechnology it is called cross-flow-microfiltration. A. S. Michaelis; Desalination 35, 329, (1980).
Although plasmapheresis represents a significant advance in the art and the concentration of certain classes of substances by ultrafiltration or hemofiltration is known, R. Schnabel; Fette-Seifen-Anstrichmittel 81 Nr. 2, 83 (1979), it has been difficult until now to achieve both a fractional and a selective separation of mixtures of certain substances. The question of selectivity is of vital importance because of so-called concentration polarization effects, by formation of secondary membranes and by interactions between the membrane and the substances being separated, the separation threshold expected because of the pore size is shifted H. Chmiel; Therapeutic Plasma Exchange; Ed. H. J. Gurland, v. Heinze, H. A. Lee; Springer, 15, (1981).
The above reference lists 560 citations relating to medicinal plasmapheresis. The separation of components of different molecular weights by cascade filtration, fractional membrane plasmapheresis, and specific membrane plasmapheresis, is discussed. cf. H. Strathmann; Chemie Technik 11 Nr. 7, 813, (1982). By connecting microfiltration membranes, ultrafiltration membranes and hyperfiltration membranes in series, it is possible to separate macromolecular substances from lower molecular weight substances.
Porous glass capillary membranes suitable for such filtration processes are described in German PS No. 2 454 111, and the use of those materials for the diafiltration of blood is described in German PS No. 2 757 673. Use of a combination of different membranes in the arrangement described is described by H. G. Sieberth in "Plasma Exchange Symposiomband," Ed. H. G. Sieberth, Schattauer Verlag 29, (1980). However, the arrangement described there in the form tested was indicated as not being practical. It is less than satisfactory in several important respects. First the membranes in vivo showed a totally different behavior as compared to the values measured in vitro. Second, albumin recovery was too low so that albumin had to be replaced and electrolyte solution (the filtrate) had to be added to the plasma in order to keep up its protein concentration constant. J. Takeda; Y. Ono; K. Yagita; Y. Sume; K. Katoka; Artificial Organs, Vo. 5 (Suppl.) 168, (1981 denominate this replacement a dilution. However, the dilution is only a three folt dilution at most.
The inadequate recovery of low molecular substances at membranes, which per se are technologically optimized, is due to the fact that filtration rates of up to 40 percent are used. If these substances are retained by the membrane or by the secondary layer which builds up on the membrane, only low recovery rates can be achieved.